Kathryn W. Tosney

    Neural Patterning

A current study in neural patterning shows that physical force may aid the exit of motor growth cones from the spinal cord. With transmission electron microscopy, we found that motor growth cones displace epithelial endfeet and spread on basal lamina well before they exit the spinal cord. During this period, the basal lamina appears intact, contrary to our expectations that it would begin to show signs of disruption and removal. Instead, the first growth cones appear to “tear” basal lamina and emerge with intact basal lamina on their surfaces. The only early indicator of exit was apparent deformations, inward and outward, of the exit zone, in accord with active physical displacement.

To determine if the deformations were indeed dynamic, an undergraduate, Amy Wagnitz, recorded initial axon exit using a semi-intact “slice culture” we devised (Hotary et al. 1996). She finds deformations are active. Moreover, they are active only during the period when growth cones are contacting the basal lamina. Deformations are absent from non-exit regions, from earlier slices before growth cones accumulate, or from later slices after growth cones have exited. Deformations are of two sorts: slow changes and rapid “twitches”. The results suggest that growth cones exert mechanical force to break through the basal lamina.

Ramon Y Cajal first likened the growth cone to a “living battering ram”, forcing its way through the embryonic environment. Although in our kinder age we tend to think of guidance in gentler terms, our evidence suggests the intriguing possibility that Cajal may have had a point.


The figure above shows two frames from a recording of a live slice taken at a level where growth cones have reached but not breached the basal lamina. Deformations at the exit zone (EZ) are indicated by arrowheads in frame D; by frame E these deformations have relaxed. Dynamic deformations such as this were present only before actual exit; earlier, as growth cones gathered at the exit zone, and later, after growth cones exited, the exit zone remained undeformed. Active deformations thus characterize the site and time when growth cones spread on the basal lamina, and are a consistent prelude to exit.


The figure below, prepared by Ken Balazovich, portrays our model of motor growth cone exit from the spinal cord.

Publications

  • Tosney, K. W. , A. Wagnitz, D. Dehnbostel, and K. J. Balazovich (2010). Evidence that growth cones exert mechanical force as they exit the spinal cord. under revision
  • Tosney, K.W., K.B. Hotary, K.B. & C.Lance-Jones (1995). Specifying the target identity of motoneurons. BioEssays, 17:379-382.
  • Schlosser, G. and K.W. Tosney (1988). Projection neurons that send axons through the lumbar spinal cord of the chick embryo are not obviously distributed in a segmentally repetitive pattern. J.Neuro.Res. 21: 410-419.
    Republished in: Neuroembryology, Cellular and Molecular Approaches.

  • Tosney, K.W. (1991). Cells and cell-interactions that guide motor axons in the developing chick embryo. BioEssays: 13:1-7.
  • Tyrell, S., S. Schroeter, L. Coulter and K.W. Tosney (1990). The distribution and projection pattern of motoneurons that innervate hindlimb muscles in the quail. J. Comp. Neurol. 298:413-430.

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